A Study of Pembrolizumab and Bavituximab in Patients With Advanced Hepatocellular Carcinoma

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This is a non-randomized, open-label, multi-site phase II therapeutic trial of pembrolizumab and bavituximab in patients with locally advanced HCC. Locally advanced or metastatic HCC is defined as disease that is not amenable to surgical and/or locoregional therapies. Subjects must not have received prior systemic therapy for advanced HCC in keeping with the first-line setting of this study.

Safety and Tolerability: rates of adverse events according to the CTCAE [ Time Frame: 36 months ]

To determine the safety and tolerability of combination pembrolizumab and bavituximab as measured by rates of adverse events according to the CTCAE

Other Outcome Measures:

Treatment response [ Time Frame: 36 months ]

To determine treatment response with pre- and intra-treatment biopsies and plasma/serum. Correlative studies will be performed on the collected tissue and blood samples to determine if predictive markers of response can be generated

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Layout table for eligibility information

Ages Eligible for Study:

18 Years and older (Adult, Older Adult)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Patient must have a histologically confirmed diagnosis hepatocellular carcinoma; known fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma and HCC will be excluded

Locally advanced or metastatic disease

Patients with locally advanced or metastatic disease must have disease deemed not amenable to surgical and/or locoregional therapies or patients who have progressed following surgical and/or locoregional therapies.

Measurable disease, as defined as lesions that can accurately be measured in at least one dimension according to RECIST version 1.1 at least 1 cm with contrast enhanced dynamic imaging (magnetic resonance imaging or computed tomography).

Child-Pugh Score A

Age ≥ 18 years

ECOG Performance score of 0-1

Life expectancy greater than 6 months

Following baseline laboratory values:

Total bilirubin ≤ 2.0 mg/ml

INR ≤ 1.7

Hgb ≥ 8.5 g/dl

AST, ALT ≤5 times ULN

Platelet count ≥ 50,000/mm3

Serum creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 50 mL/min

Albumin ≥ 2.5 g/dl

Absolute neutrophil ≥ 1,500 cells/mm3

Male and female subjects of child bearing potential must agree to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication

Women of childbearing potential must have a negative pregnancy test within 72 hours prior to receiving the first dose of study medication

Subjects are eligible to enroll if they have non-viral-HCC, or if they have HBV-HCC, or HCV-HCC defined as follows:

HBV-HCC: Controlled (treated) hepatitis B subjects will be allowed if they meet the following criteria:

Antiviral therapy for HBV must be given for at least 12 weeks and HBV viral load must be less than 100 IU/mL prior to first dose of study drug. Subjects on active HBV therapy with viral loads under 100 IU/ml should stay on the same therapy throughout study treatment.

Subjects who are anti-HBc (+), negative for HBsAg, negative for anti-HBs, and have an HBV viral load under 100 IU/mL do not require HBV anti-viral prophylaxis.

HCV-HCC: active or resolved HCV infection as evidenced by detectable HCV RNA or antibody. Patients who have failed HCV therapy as evidenced by detectable HCV RNA will be eligible. Subjects with chronic infection by HCV who are treated (successfully or treatment failure) or untreated are allowed on study. In addition, subjects with successful HCV treatment are allowed as long as there are ≥4 weeks between completion of HCV therapy and start of study drug.

Successful HCV treatment definition: SVR12.

- Prior therapy is allowed provided the following are met: at least 4 weeks since prior locoregional therapy including surgical resection, chemoembolization, radiotherapy, or ablation. Provided target lesion has increased in size by 25% or more or the target lesion was not treated with locoregional therapy. Patients treated with palliative radiotherapy for symptoms will be eligible 1 week after treatment as long as the target lesion is not the treated lesion.

Exclusion Criteria:

Prior liver transplant;

Patient who has received previous systemic therapy for HCC;

Clinically significant, uncontrolled heart disease and/or recent events including any of the following:

Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication;

Active, known, or suspected autoimmune disease with the following exceptions i) Subjects with vitiligo, type I diabetes mellitus, resolved childhood asthma or atopy are permitted to enroll; ii) Subjects with suspected autoimmune thyroid disorders may be enrolled if they are currently euthyroid or with residual hypothyroidism requiring only hormone replacement.

iii) Subjects with psoriasis requiring systemic therapy must be excluded from enrollment

Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg/day prednisone equivalent) or other immunosuppressive medications within 14 days of study administration. Inhaled or topical steroids and adrenal replacement doses >10 mg/day prednisone equivalents are permitted in the absence of autoimmune disease;

Patient who has received radiotherapy ≤ 4 weeks prior to study entry. Palliative radiotherapy for symptomatic control is acceptable (if completed at least 2 weeks prior to study drug administration and no additional radiotherapy for the same lesion is planned);

Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered as major surgery);